Botulism toxins are produced by the bacteria Clostridium botulinum, C. butyricum, C. baratii and C. argentinense. Foodborne botulism can be transmitted through food that has not been heated correctly prior to being canned or food that was not cooked correctly from a can. Most infant botulism cases cannot be prevented because the bacteria that cause this disease are in soil and dust. The bacteria can be found inside homes on floors, carpet, and countertops even after cleaning. Food-borne botulism usually results from ingestion of food that has become contaminated with spores (such as a perforated can) in an anaerobic environment, allowing the spores to germinate and grow. The growing (vegetative) bacteria produce toxin. It is the ingestion of toxin that causes botulism, not the ingestion of the spores or the vegetative bacteria. Infant and wound botulism both result from infection with spores, which subsequently germinate, resulting in production of toxin and the symptoms of botulism.
Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. Botulinum toxin can be absorbed from eyes, mucous membranes, respiratory tract or non-intact skin. It is the most acutely toxic substance known, with an estimated human median lethal dose of 1.3-2.1 ng/kg intravenously or intramuscularly and 10-13 ng/kg when inhaled. Botulinum neurotoxin (BoNT) intoxication results in a severe and potentially fatal neurological disease characterized by acute flaccid paralysis of motor and autonomic nerves. Human disease results from toxins produced by four serotypes of Clostridium botulinum: A, B, E, and F. Though botulinum poisoning is rare, the Center for Disease Control (CDC) has identified botulinum toxin as one of the six biggest threats for a bioterrorist attack on the United States of America. Currently, the only treatment for BoNT poisoning is delivery of an anti-serum, however, this requires rapid identification of BoNT poisoning as well as weeks to months of supportive care. The effectiveness of BoNT antiserum demonstrates that a BoNT vaccine inducing neutralizing antibodies can prevent disease upon exposure. An experimental pentavalent toxoid (A, B, C, D, E) vaccine previously available to military personnel and individuals employed in laboratory and manufacturing settings, who work with neurotoxin-producing species of Clostridium, has been discontinued by the CDC due to limited effectiveness and tolerability issues. In addition, a bivalent (A, B) recombinant toxoid vaccine is under investigation.
Accordingly, there remains a need for effective BoNT vaccines that produce broad immunity against one or more serotypes of Clostridium botulinum, including in particular, serotypes A, B, E, and/or F, and preferably, a universal vaccine that would be globally effective.